A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity
18 Years
N/A
Both
Colorectal Cancer, Neurotoxicity
Trial Information
A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity
OBJECTIVES:
- Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent
or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients
receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer.
- Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can
be delivered without chronic neurotoxicity.
- Determine whether CaMg infusions can ameliorate the acute neuropathy associated with
oxaliplatin.
- Determine whether CaMg infusions cause any adverse events.
- Investigate whether CaMg infusions influence quality of life, fatigue, and activities
of daily living of these patients.
- Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced
neurotoxicity.
OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
are stratified according to age (< 65 vs > 65), gender, and chemotherapy regimen (FOLFOX4 vs
modified FOLFOX6). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes
immediately before and after each oxaliplatin administration (once every 2 weeks) of
their assigned chemotherapy regimen.
- Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each
oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
In both arms, treatment continues until chemotherapy is discontinued (approximately 6
months).
Patients complete quality of life questionnaires on day 1, a symptom experience diary on
days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after
completion of study treatment.
Blood samples are collected at baseline and tested for the GSTP1 gene.
After completion of study treatment, patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the colon or rectum
- Stage II disease
- Stage III disease
- Stage IV disease (completely resected with no evidence of residual tumor)
- Must have undergone curative resection for stage II or III disease
- Scheduled to receive 6 months of adjuvant treatment with either of the following
FOLFOX chemotherapy regimens:
- FOLFOX4, comprising leucovorin calcium, fluorouracil, and oxaliplatin (2-week
course)
- Modified FOLFOX6, comprising high-dose leucovorin calcium, high-dose
fluorouracil, and oxaliplatin (2-week course)
PATIENT CHARACTERISTICS:
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- WBC ≥ 3,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN
- Calcium normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No pre-existing peripheral neuropathy of any grade
- No hypercalcemia
- No concurrent heart block or a history of heart block
- No other medical condition that, in the opinion of the treating physician, would make
this protocol unreasonably hazardous for the patient
- No family history of a genetic/familial neuropathy
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin,
taxanes, or vinca alkaloids
- Concurrent use of bevacizumab or cetuximab in combination with FOLFOX as part of a
clinical trial or clinical practice are allowed
- No concurrent digitalis medication
- No concurrent digoxin
- No concurrent treatment with anticonvulsants such as carbamazepine, phenytoin, or
valproic acid
- No other concurrent neurotropic agents such as gabapentin
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Outcome Measure:
Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event
Outcome Description:
Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)
Outcome Time Frame:
127 days
Safety Issue:
Yes
Principal Investigator
Charles L. Loprinzi, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000471238
NCT ID:
NCT00316914
Start Date:
January 2006
Completion Date:
November 2012
Related Keywords:
- Colorectal Cancer
- Neurotoxicity
- neurotoxicity
- stage II colon cancer
- stage III colon cancer
- adenocarcinoma of the colon
- stage II rectal cancer
- stage III rectal cancer
- stage IV rectal cancer
- stage IV colon cancer
- adenocarcinoma of the rectum
- Colorectal Neoplasms
- Neurotoxicity Syndromes
Name | Location |
|---|---|
| CCOP - Iowa Oncology Research Association | Des Moines, Iowa 50309-1016 |
| Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls, South Dakota 57117-5039 |
| Medical X-Ray Center, PC | Sioux Falls, South Dakota 57105 |
| Avera Cancer Institute | Sioux Falls, South Dakota 57105 |
| John Stoddard Cancer Center at Iowa Methodist Medical Center | Des Moines, Iowa 50309 |
| MBCCOP - Medical College of Georgia Cancer Center | Augusta, Georgia 30912-3730 |
| John Stoddard Cancer Center at Iowa Lutheran Hospital | Des Moines, Iowa 50316-2301 |
| Mercy Capitol Hospital | Des Moines, Iowa 50307 |
| Medical Oncology and Hematology Associates at John Stoddard Cancer Center | Des Moines, Iowa 50309 |
| Medical Oncology and Hematology Associates at Mercy Cancer Center | Des Moines, Iowa 50314 |
| Mercy Cancer Center at Mercy Medical Center - Des Moines | Des Moines, Iowa 50314 |
| Bismarck Cancer Center | Bismarck, North Dakota 58501 |
| Mid Dakota Clinic, PC | Bismarck, North Dakota 58501 |
| Medcenter One Hospital Cancer Care Center | Bismarck, North Dakota 58501 |
